Frequent Mutations in p53, CDKN2A, PTEN Genes in Lung Squamous Cell Carcinoma: A Next Generation Sequencing Study

Abstract

Abstract Introduction/Objective Targeted therapies have been successfully used for the treatment of lung adenocarcinoma but have not been implemented in the treatment of lung squamous cell carcinoma (SqCC). In order to better understand the underlying biology of SqCC, we present comprehensive Next Generation Sequencing (NGS) data via Cancerplex from SqCC. We have observed frequent mutations in p53, CDKN2A, PTEN, CDKN2B, and TGFBR2 genes together with few new rare gene mutations. Methods Twenty-one patients with diagnosis of Lung SqCC have been selected for Cancerplex assay (Kew, Inc., Waltham, MA). Formalin-fixed tissues from these patients were used for the assay. Neoplastic tissues with tumor content higher than 20% were micro-dissected from the blocks and NGS was performed with at least 50 ng DNA content and with a limit of detection of 10% mutant alleles. The depth of coverage was 500, and the size of the targeted region was 2.8 Mb. Results were compared with published databases. Results We have observed p53 mutations in 100% cases. p53 gene mutations included single point mutations with various coding protein mutations as well as splice variants. Mutations in CDKN2A is found in 47.6% of cases; PTEN mutations in 33.3% of cases; CDKN2B mutations in 28.6% of cases, and TGFBR2 in 28.6% of cases, which has been reported as actionable variants and actionable copy number variants. Conclusion Previous literatures have provided evidence that SqCC arising in different anatomical sites share common genomic mutation patterns. Our data partially supports this finding. We demonstrated p53, CDKN2A and PTEN are among the most commonly mutated genes in lung SqCC, while a few other genes mutations does not fit in this pattern. Apparently more studies need to be done to provide a more clear genetic landscape of SqCC, which would facilitate the development of targeted therapies.